Abstract

ObjectivesBreast malignancy is a serious threat to women’s health around the world. Following the rapid progress in the field of cancer diagnostics and identification of pathological markers, breast tumor treatment methods have been greatly improved. However, for invasive, ductal carcinomas and mammary fibroadenoma, there is an urgent demand for better breast tumor-linked biomarkers. The current study was designed to identify diagnostic and/or therapeutic protein biomarkers for breast tumors.MethodsA total of 140 individuals were included, comprising 35 healthy women, 35 invasive breast cancers (IBC), 35 breast ductal carcinomas in situ (DCIS), and 35 breast fibroadenoma patients. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to characterize differentially expressed proteins for potential biomarkers in IBC, DCIS, and fibroadenomas by comparisons with their matched adjacent tissues and/or normal breast tissues. The public databases Metascape and String were used for bioinformatic analyses.ResultsUsing the proteomics approach, we identified differentially expressed proteins in tissues of different breast tumors compared to normal/adjacent breast tissues, including 100 in IBC, 52 in DCIS, and 44 in fibroadenoma. Among the 100 IBC differentially expressed proteins, 37 were found to be specific to this type of cancer only. Additionally, four proteins were specifically expressed in DCIS and four in fibroadenoma. Compared to corresponding adjacent tissues and normal breast tissues, 18 step-changing proteins were differentially expressed in IBC, 14 in DCIS, and 13 in fibroadenoma, respectively. Compared to DCIS and normal breast tissues, 65 proteins were differentially expressed in IBC with growing levels of malignancy.ConclusionsThe identified potential protein biomarkers may be used as diagnostic and/or therapeutic targets in breast tumors.

Highlights

  • Breast cancer is the most common female malignancy and one of the primary causes of the cancer-associated morbidity and mortality [1]

  • We identified invasive breast cancers (IBC)-linked 20 upregulated proteins compared to both adjacent and normal tissues (Supplementary Table 1)

  • In the analysis of step-changing proteins, we identified seven proteins that were increased in IBC tissues compared to the IBC-adjacent and normal tissues (Supplementary Table 3)

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Summary

Introduction

Breast cancer is the most common female malignancy and one of the primary causes of the cancer-associated morbidity and mortality [1]. The Global Cancer Statistics estimated 268,600 new breast cancer cases and 41,760 deaths in the United States in 2019 [1]. Fibroadenoma is a benign fibroepithelial tumor and is one of the most common breast masses [2], often detected in young females [3, 4]. Breast tumor diagnostics rely mainly on pathological techniques [5, 6]. According to the histopathological findings, breast cancer treatment usually proceeds toward surgical management, followed in most cases by chemotherapies [7]. The choice of chemotherapies is often complicated by the heterogeneity of the cancers [8]

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